We are requesting partial support for a FASEB Conference on "Post-Transcriptional Regulation of Gene Expression: Mechanisms of mRNA Decay", to be held in Snowmass Village, CO on June 24-29, 2006. Turnover of mRNA is a key, but frequently unrecognized, regulator of gene expression. The stability of an mRNA dictates its ultimate steady-state level. Programmed instability is an important mechanism of repressing gene expression, and the surveillance of mRNA quality ensures that only "fit" transcripts exit the nucleus and are translated, while RNA interference relies on selective mRNA turnover for its biological consequences, whereas novel pharmaceuticals are targeting mRNA decay pathways. For these reasons, mRNA turnover is attracting heightened interest from all areas of the life sciences. The proposed FASEB Conference is unique in concentrating on mRNA decay, thereby exploring in diverse biological settings the mechanisms, both at the cellular and molecular levels that underpin this universal process. The proposed meeting is particularly noteworthy in attracting investigators who study both prokaryotic and eukaryotic organisms, and in focusing on mechanisms by which RNAs interact with the decay apparatus, the translation apparatus, and the factors which modulate decay. The meeting's sessions will address decay events specific for mRNA 5'or 3'termini and their subcellular localization;structure/function relationships in RNA binding proteins, small RNAs, and other decay factors;the interplay of mRNA decay with the processes of translation and transcription;RNA quality control and related regulatory networks;and the clinical and pharmaceutical relevance of mRNA decay. It is anticipated that the presentations at the meeting will include the first public disclosures of several key structures and mechanisms, as well as provide novel insights for the regulation of growth, development, and disease. In short, the conference will provide an overview of the latest progress in an exciting field and will propel the next stage of its development.